High glucose induces senescence in synovial mesenchymal stem cells through mitochondrial dysfunction

Area of Science:

• Cell Biology
• Stem Cell Biology
• Mitochondrial Biology

Background:

• Synovial mesenchymal stem cells (SMSCs) play a crucial role in joint health and tissue repair.
• High glucose conditions, characteristic of diabetes, are known to induce cellular stress and dysfunction.
• Understanding how high glucose affects SMSCs is vital for developing treatments for related pathologies.

Purpose of the Study:

• To investigate the impact of high glucose on SMSC senescence.
• To elucidate the role of mitochondrial dysfunction in high glucose-induced SMSC senescence.
• To explore the potential for glucose normalization to reverse these effects.

Main Methods:

• SMSCs were exposed to high glucose (25 mmol/L) or low glucose (5.5 mmol/L) for varying durations (24h, 48h).
• Assessed proliferation, senescence markers (SASP genes, SA-β-gal activity), mitochondrial ROS, mitochondrial fission, and mitophagy.
• Investigated the reversibility of high glucose effects by switching to low glucose medium.

Main Results:

• High glucose accelerated SMSC senescence, evidenced by increased SASP gene expression and SA-β-gal-positive cells.
• Elevated mitochondrial ROS, increased mitochondrial fission, and suppressed mitophagy (reduced PINK1, PARKIN, LC3B) were observed.
• Effects of high glucose, including suppressed gene/protein expression and increased oxidative stress, were reversible upon glucose normalization.

Conclusions:

• High glucose induces SMSC senescence through mitochondrial dysfunction, characterized by ROS accumulation, excessive fission, and mitophagy inhibition.
• Glucose normalization effectively reversed senescence phenotypes, restoring mitophagy and reducing oxidative stress.
• Mitochondrial dysfunction is a key mechanism in high glucose-induced SMSC senescence.